Podium 1: Skeletal Disorders, Treatments & Rehabilitation
Direct Infused Lentiviral Gene Therapy For Morquio Syndrome In A Histo-Pathological Perspective
Betul Celik, Estera Rintz, Nidhi FNU, Andres Felipe Leal, Shaukat Khan, Shunji Tomatsu
Nemours Children’s Health System
Morquio syndrome is an autosomal recessive disease caused by a mutation in the N-acetylgalactosamine-6-sulfate sulfatase gene. No effective treatment for this skeletal disease is present. Therefore, a novel therapy is an unmet challenge to reverse or ameliorate the disease progression. We hypothesized that the proposed novel lentiviral vectors (LV) could permanently produce the active enzyme by transduced cells into the circulation and would significantly impact bone and cartilage abnormalities in mice with Morquio. LVs carrying the native GALNS gene were produced under three different promoters (ubiquitous-CBh, collagen type II-COL2A1, hematopoietic stem cells-CD11b). Then, we treated GALNS knockout (KO) mice intravenously at newborns and 4 weeks old with low/high doses of LVs under three different promoters. Blood samples were collected biweekly following direct in vivo infusion, and mice were autopsied at 16 weeks old to collect tissues. We aimed to investigate vector copy number, enzyme activity levels and the GAG concentrations in blood and tissue samples, plasma AST/ALT levels, pathology, and bone morphology. In vivo experiment data demonstrated that LVs under ubiquitous CBh promoter with high dose in KO newborn mice had the highest enzyme activity. Bone pathology showed little impact of the LV treatment in bone.
Research Area: Bone